Increased risk of oral contraceptive failure with nelfinavir

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HIV-positive women taking oral contraceptives and the protease inhibitor nelfinavir are significantly more likely to experience contraceptive failure and become pregnant, according to a retrospective United States study published in the September 1st edition of the Journal of Acquired Immune Deficiency Syndromes. The Investigators, in New Orleans, recommend that women taking nelfinavir should use additional contraceptive methods.

Significant interactions between most protease inhibitors or non-nucleoside reverse transcriptase inhibitors (NNRTIs) and oral contraceptives containing ethinyl oestradiol and norethindrone has long been recognised, and women taking most protease inhibitors or NNRTIs are recommended not to rely on oral contraception.

The incidence of oral contraceptive failure amongst women taking highly active antiretroviral therapy (HAART) has not, however, been examined. Accordingly, investigators conducted a retrospective review of the records of 2053 HIV-positive women who received care at an HIV clinic in New Orleans between 1997 and 2002.

Glossary

oral

Refers to the mouth, for example a medicine taken by mouth.

retrospective study

A type of longitudinal study in which information is collected on what has previously happened to people - for example, by reviewing their medical notes or by interviewing them about past events. 

reverse transcriptase

A retroviral enzyme which converts genetic material from RNA into DNA, an essential step in the lifecycle of HIV. Several classes of anti-HIV drugs interfere with this stage of HIV’s life cycle: nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). 

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

A total of 41 women were identified as being pregnant and taking oral contraceptives in the same six-month period. Further analysis revealed that eleven of these women became pregnant whilst using oral contraceptives.

When the investigators looked at the antiretrovirals prescribed to the women using oral contraceptives they found that women taking nelfinavir were significantly more likely to become pregnant (p < 0.05) and that women prescribed indinavir were significantly less likely to become pregnant (p < 0.05).

These results were consistent with known pharmacological interactions between protease inhibitors and oral contraceptives. Nelfinavir reduces levels of norethindrone by 18% and levels of ethinyl estradiol by 47%. By contrast, indinavir increases levels of norethindrone by 26% and levels of ethinyl estradiol by 24%.

"Women taking nelfinavir should use additional or alternative contraceptive methods", conclude the investigators.

References

Clark RA et al. Population-based study evaluating association between selected antiretroviral therapies and potential oral contraceptive failure. J Acquir Immune Defic Syndr 37: 1219-1220, 2004.